tbuckley/cabot-search huggingface dataset:
The role of ovarian hormones in the pathophysiology of perimenopausal sleep disturbances: A systematic review
Authors: Annika Haufe, Fiona C. Baker, Brigitte Leeners
Journal: Sleep Medicine Reviews (2022)

Sleep disturbance is a common clinical concern throughout the menopausal transition. However, the pathophysiology and causes of these sleep disturbances remain poorly understood, making it challenging to provide appropriate therapy. Our goal was to i) review the literature about the influence of ovarian hormones on sleep in perimenopausal women, ii) summarize the potential underlying pathophysiology of menopausal sleep disturbances and iii) evaluate the implications of these findings for the therapeutic approach to sleep disturbances in the context of menopause. A systematic literature search using the databases Embase, MEDLINE and Cochrane Library was conducted. Keywords relating to ovarian hormones, sleep disturbances and menopause were used. Ultimately, 86 studies were included. Study Quality Assessment Tools of the National Institutes of Health were used for quality assessment. Results from good-quality studies demonstrated that the postmenopausal decline in estrogen and progesterone contributes to sleep disturbances in women and that timely treatment with estrogen and/or progesterone therapy improved overall sleep quality. Direct and indirect effects of both hormones acting in the central nervous system and periphery, as well as via secondary effects (e.g. reduction in vasomotor symptoms), can contribute to improvements in sleep. To strengthen external validity, studies examining neurobiological pathways are needed.
Recent advancements in microneedle-based vaccine delivery
Authors: Jobin Jose, Kartik Bhairu Khot, Prajna Shastry, Gopika Gopan, Akshay Bandiwadekar, Simi P. Thomas, Sabith T Muhammad, Sanjay R. Ugare, Hitesh Chopra, None Priyanka, Om Prakash Choudhary
Journal: International Journal of Surgery (2022)
Monkeypox lineages amid the ongoing COVID-19 pandemic: A global public health concern – Correspondence
Authors: Ranjan K. Mohapatra, Venkataramana Kandi, Veronique Seidel, Ashish K. Sarangi, Snehasish Mishra, Ali A. Rabaan, Saad Alhumaid, Abbas Al Mutair, Kuldeep Dhama
Journal: International Journal of Surgery (2022)
Comparison of Drug-Coated Balloons vs Bare-Metal Stents in Patients With Femoropopliteal Arterial Disease
Authors: Mehdi H. Shishehbor, Dierk Scheinert, Ashit Jain, Marianne Brodmann, Gunnar Tepe, Kenji Ando, Prakash Krishnan, Osamu Iida, John R. Laird, Peter A. Schneider, Krishna J. Rocha-Singh, Thomas Zeller
Journal: Journal of the American College of Cardiology (2022)

Endovascular treatment of femoropopliteal artery disease has shifted toward drug-coated balloons (DCB). However, limited data are available regarding the safety and efficacy of DCB vs bare-metal stents (BMS). The purpose of this study was to compare DCB vs BMS outcomes in a propensity-adjusted, pooled analysis of 4 prospective, multicenter trials. Patient-level data were pooled from 4 prospective, multicenter studies: the IN.PACT SFA I/II and IN.PACT SFA Japan randomized controlled DCB trials and the Complete SE and DURABILITY II single-arm BMS studies. Outcomes were compared using inverse probability of treatment weighting (IPTW). Clinical endpoints were 12-month primary patency, freedom from 36-month clinically driven target lesion revascularization, and cumulative 36-month major adverse events (MAE). The primary analysis included 771 patients (288 DCB, 483 BMS). IPTW-adjusted demographic, baseline lesion, and procedural characteristics were matched between groups. The adjusted mean lesion length was 8.1 ± 4.7 cm DCB and 7.9 ± 4.5 cm BMS. The IPTW-adjusted Kaplan-Meier estimates of 12-month primary patency (90.4% DCB, 80.9% BMS, P = 0.007), freedom from 36-month clinically driven target lesion revascularization (85.6% DCB, 73.7% BMS, P = 0.001), and cumulative incidence of 36-month MAE (25.3% DCB, 38.8% BMS, P < 0.001) favored DCB. There were no statistically significant differences observed in all-cause mortality, target limb major amputation, or thrombosis through 36 months. In a patient-level, IPTW-adjusted pooled analysis of prospective, multicenter pivotal studies, DCB demonstrated significantly higher patency, lower revascularization and MAE rates, and no statistically significant differences in mortality, amputation, or thrombosis vs BMS. This analysis supports DCB use vs BMS in moderately complex femoropopliteal lesions amenable to both treatments.
FDA's authorized “JYNNEOS” vaccine for counteracting monkeypox global public health emergency; an update – Correspondence
Authors: Ranjit Sah, Mahnoor Humayun, Eesha Baig, Minaam Farooq, Huzaifa Ghulam Hussain, Muhammad Usama Shahid, Huzaifa Ahmad Cheema, Deepak Chandran, Mohd Iqbal Yatoo, Anil K. Sharma, Kuldeep Dhama
Journal: International Journal of Surgery (2022)
PlantCADB: A Comprehensive Plant Chromatin Accessibility Database
Authors: Ke Ding, Shanwen Sun, Yang Luo, Chaoyue Long, Jingwen Zhai, Yixiao Zhai, Guohua Wang
Journal: Genomics Proteomics & Bioinformatics (2022)

Chromatin accessibility landscapes are essential for detecting regulatory elements, illustrating the corresponding regulatory networks, and, ultimately, understanding the molecular basis underlying key biological processes. With the advancement of sequencing technologies, a large volume of chromatin accessibility data has been accumulated and integrated for humans and other mammals. These data have greatly advanced the study of disease pathogenesis, cancer survival prognosis, and tissue development. To advance the understanding of molecular mechanisms regulating plant key traits and biological processes, we developed a comprehensive plant chromatin accessibility database (PlantCADB) from 649 samples of 37 species. These samples are abiotic stress-related (such as heat, cold, drought, and salt; 159 samples), development-related (232 samples), and/or tissue-specific (376 samples). Overall, 18,339,426 accessible chromatin regions (ACRs) were compiled. These ACRs were annotated with genomic information, associated genes, transcription factor footprint, motif, and single-nucleotide polymorphisms (SNPs). Additionally, PlantCADB provides various tools to visualize ACRs and corresponding annotations. It thus forms an integrated, annotated, and analyzed plant-related chromatin accessibility resource, which can aid in better understanding genetic regulatory networks underlying development, important traits, stress adaptations, and evolution.PlantCADB is freely available at https://bioinfor.nefu.edu.cn/PlantCADB/.
The epigenetic state of IL-4-polarized macrophages enables inflammatory cistromic expansion and extended synergistic response to TLR ligands
Authors: Zsolt Czimmerer, Laszlo Halasz, Bence Daniel, Zsofia Varga, Krisztian Bene, Apolka Domokos, Marten Hoeksema, Zeyang Shen, Wilhelm K. Berger, Timea Cseh, Karoly Jambrovics, Zsuzsanna Kolostyak, Ferenc Fenyvesi, Judit Varadi, Szilard Poliska, Gyorgy Hajas, Istvan Szatmari, Christopher K. Glass, Attila Bacsi, Laszlo Nagy
Journal: Immunity (2022)

Prior exposure to microenvironmental signals could fundamentally change the response of macrophages to subsequent stimuli. It is believed that T helper-2 (Th2)-cell-type cytokine interleukin-4 (IL-4) and Toll-like receptor (TLR) ligand-activated transcriptional programs mutually antagonize each other, and no remarkable convergence has been identified between them. In contrast, here, we show that IL-4-polarized macrophages established a hyperinflammatory gene expression program upon lipopolysaccharide (LPS) exposure. This phenomenon, which we termed extended synergy, was supported by IL-4-directed epigenomic remodeling, LPS-activated NF-κB-p65 cistrome expansion, and increased enhancer activity. The EGR2 transcription factor contributed to the extended synergy in a macrophage-subtype-specific manner. Consequently, the previously alternatively polarized macrophages produced increased amounts of immune-modulatory factors both in vitro and in vivo in a murine Th2 cell-type airway inflammation model upon LPS exposure. Our findings establish that IL-4-induced epigenetic reprogramming is responsible for the development of inflammatory hyperresponsiveness to TLR activation and contributes to lung pathologies.
Fucoidan and topography modification improved in situ endothelialization on acellular synthetic vascular grafts
Authors: Yuan Yao, Aung Moe Zaw, Deirdre E.J. Anderson, YeJin Jeong, Joshua Kunihiro, Monica T. Hinds, Evelyn K.F. Yim
Journal: Bioactive Materials (2022)

Thrombogenesis remains the primary failure of synthetic vascular grafts. Endothelial coverage is crucial to provide an antithrombogenic surface. However, most synthetic materials do not support cell adhesion, and transanastomotic endothelial migration is limited. Here, a surface modification strategy using fucoidan and topography was developed to enable fast
Gut colonization by Proteobacteria alters host metabolism and modulates cocaine neurobehavioral responses
Authors: Santiago Cuesta, Paula Burdisso, Amir Segev, Saïd Kourrich, Vanessa Sperandio
Journal: Cell Host & Microbe (2022)

Gut-microbiota membership is associated with diverse neuropsychological outcomes, including substance use disorders (SUDs). Here, we use mice colonized with Citrobacter rodentium or the human γ-Proteobacteria commensal Escherichia coli HS as a model to examine the mechanistic interactions between gut microbes and host responses to cocaine. We find that cocaine exposure increases intestinal norepinephrine levels that are sensed through the bacterial adrenergic receptor QseC to promote intestinal colonization of γ-Proteobacteria. Colonized mice show enhanced host cocaine-induced behaviors. The neuroactive metabolite glycine, a bacterial nitrogen source, is depleted in the gut and cerebrospinal fluid of colonized mice. Systemic glycine repletion reversed, and γ-Proteobacteria mutated for glycine uptake did not alter the host response to cocaine. γ-Proteobacteria modulated glycine levels are linked to cocaine-induced transcriptional plasticity in the nucleus accumbens through glutamatergic transmission. The mechanism outline here could potentially be exploited to modulate reward-related brain circuits that contribute to SUDs.
(+)/(−)-Yanhusamides A−C, three pairs of unprecedented benzylisoquinoline-pyrrole hetero-dimeric alkaloid enantiomers from Corydalis yanhusuo
Authors: Lingyan Wang, Guiyang Xia, Huan Xia, Xiaohong Wei, Yanan Wang, Sheng Lin
Journal: Acta Pharmaceutica Sinica B (2022)

A chemical investigation on the aqueous extract of Corydalis yanhusuo tubers led to the isolation and structural elucidation of three pairs of trace enantiomeric hetero-dimeric alkaloids, (+)/(-)-yanhusamides A-C (1-3), featuring an unprecedented 3,8-diazatricylco[5.2.2.02,6]undecane-8,10-diene bridged system. Their structures were exhaustively characterized by X-ray diffraction, comprehensive spectroscopic data analysis, and computational methods. Guided by the hypothetical biosynthetic pathway for 1-3, a gram-scale biomimetic synthesis of (±)-1 was achieved in 3 steps using photoenolization/Diels-Alder (PEDA) [4+2] cycloaddition. Compounds 1‒3 exhibited potent inhibition of NO production induced by LPS in RAW264.7 macrophages. The in vivo assay showed that oral administration of 30 mg/kg of (±)-1 attenuated the severity of rat adjuvant-induced arthritis (AIA). Additionally, (±)-1 induced a dose-dependent antinociceptive effect in the acetic acid-induced mice writhing assay.
Deep tissue infection by an invasive human fungal pathogen requires lipid-based suppression of the IL-17 response
Authors: Pauline Basso, Eric V. Dang, Anatoly Urisman, Leah E. Cowen, Hiten D. Madhani, Suzanne M. Noble
Journal: Cell Host & Microbe (2022)

Candida albicans is the most common cause of fungal infection in humans. IL-17 is critical for defense against superficial fungal infections, but the role of this response in invasive disease is less understood. We show that C. albicans secretes a lipase, Lip2, that facilitates invasive disease via lipid-based suppression of the IL-17 response. Lip2 was identified as an essential virulence factor in a forward genetic screen in a mouse model of bloodstream infection. Murine infection with C. albicans strains lacking Lip2 display exaggerated IL-17 responses that lead to fungal clearance from solid organs and host survival. Both IL-17 signaling and lipase activity are required for Lip2-mediated suppression. Lip2 inhibits IL-17 production indirectly by suppressing IL-23 production by tissue-resident dendritic cells. The lipase hydrolysis product, palmitic acid, similarly suppresses dendritic cell activation in vitro. Thus, C. albicans suppresses antifungal IL-17 defense in solid organs by altering the tissue lipid milieu.
MGAT2 inhibitor decreases liver fibrosis and inflammation in murine NASH models and reduces body weight in human adults with obesity
Authors: Dong Cheng, Bradley A. Zinker, Yi Luo, Petia Shipkova, Claudia H. De Oliveira, Gopal Krishna, Elizabeth A. Brown, Stephanie L. Boehm, Giridhar S. Tirucherai, Huidong Gu, Zhengping Ma, Ching-Hsuen Chu, Joelle M. Onorato, Lisa M. Kopcho, Ron Ammar, Julia Smith, Pratik Devasthale, R. Michael Lawrence, Steven A. Stryker, Elizabeth A. Dierks, Anthony V. Azzara, Leon Carayannopoulos, Edgar D. Charles, Kimberley A. Lentz, David A. Gordon
Journal: Cell Metabolism (2022)
Essential medicines for childhood cancer in Europe: a pan-European, systematic analysis by SIOPE
Authors: Maria Otth, Eva Brack, Pamela R Kearns, Olga Kozhaeva, Marko Ocokoljic, Reineke A Schoot, Gilles Vassal, Federica Achini, Adriana Balduzzi, Maja Beck Popovic, Auke Beishuizen, Luca Bergamaschi, Andrea Biondi, Franck Bourdeaut, Elena Braicu, Jesper Brok, Laurence Brugières, Amos Burke, Gabriele Calaminus, Michela Casanova, Marie-Louise Choucair, Morgane Cleirec, Selim Corbaciouglu, Maria Genoveva Correa Llano, Teresa De Rojas, Nerea Domínguez Pinilla, Caroline Elmaraghi, Andrea Ferrari, Alexander Fossa, Nathalie Gaspar, Nikolas Herold, Kyriaki Karapiperi, Maarja Karu, Mimi Kjærsgaar, Fabian Knörr, Christa Koenig, Izabela Kranjcec, Malgorzata Krawczyk, Kai Lehmberg, Thomas Lehrnbecher, Maaike Lunesink, Davide Massano, Nuša Matijasic, Hans Merks, Markus Metzler, Anthony Michalski, Milen Minkov, Bruce Morland, Naghmeh Niktoreh, Elena Oltenau, Daniel Orbach, Cormac Owens, Smaragda Papachristidou, Claudia Pasqualini, Maja Pavlovic, Paula Perez Albert, Fiona Poyer, Ivana Radulovic, Dirk Reinhardt, Joana Rebelo, Eva Roser, Ida Russo, Katrin Scheinemann, Christina Schindera, Martin Schrappe, Astrid Sehested, Jalid Sehouli, Filippo Spreafico, Sandra J Strauss, Janine Stutterheim, Karel Svojgr, Vasiliki Tzotzola, Roelof Van Ewijk, Arnauld Verschuur, Ajay Vora, Willi Woessmann, Olga Zajac-Spychala, Michel Zwaan
Journal: The Lancet Oncology (2022)
Alzheimer’s dementia or Alzheimer’s disease – What’s the difference and why should we care?
Authors: Daniel M. Gibbs
Journal: Ageing Research Reviews (2022)

• Alzheimer's dementia represents only the last few years of Alzheimer's disease. • Alzheimer's disease includes up to 20 years of pre-symptomatic disease. • The pre-symptomatic stage may be the most effective time to attack the disease.
Elevated Hypothalamic TCPTP in Obesity Contributes to Cellular Leptin Resistance
Authors: Kim Loh, Atsushi Fukushima, Xinmei Zhang, Sandra Galic, Dana Briggs, Pablo J. Enriori, Stephanie Simonds, Florian Wiede, Alexander Reichenbach, Christine Hauser, Natalie A. Sims, Kendra K. Bence, Sheng Zhang, Zhong-Yin Zhang, Barbara B. Kahn, Benjamin G. Neel, Zane B. Andrews, Michael A. Cowley, Tony Tiganis
Journal: Cell Metabolism (2022)
Functional biomaterials for comprehensive periodontitis therapy
Authors: Jiayi Luan, Ruotao Li, Weiguo Xu, Huiying Sun, Qiqi Li, Di Wang, Shujun Dong, Jianxun Ding
Journal: Acta Pharmaceutica Sinica B (2022)

Periodontitis is an inflammatory disease caused by bacterial infection directly, and the dysregulation of host immune-inflammatory response finally destroys periodontal tissues. Current treatment strategies for periodontitis mainly involve mechanical scaling/root planing (SRP), surgical procedures, and systemic or localized delivery of antimicrobial agents. However, SRP or surgical treatment alone has unsatisfactory long-term effects and is easy to relapse. In addition, the existing drugs for local periodontal therapy do not stay in the periodontal pocket long enough and have difficulties in maintaining a steady, effective concentration to obtain a therapeutic effect, and continuous administration always causes drug resistance. Many recent studies have shown that adding bio-functional materials and drug delivery systems upregulates the therapeutic effectiveness of periodontitis. This review focuses on the role of biomaterials in periodontitis treatment and presents an overview of antibacterial therapy, host modulatory therapy, periodontal regeneration, and multifunctional regulation of periodontitis therapy. Biomaterials provide advanced approaches for periodontal therapy, and it is foreseeable that further understanding and applications of biomaterials will promote the development of periodontal therapy.
The impact of lipids on the cancer–immunity cycle and strategies for modulating lipid metabolism to improve cancer immunotherapy
Authors: Mingming Zheng, Wenxin Zhang, Xi Chen, Hongjie Guo, Honghai Wu, Yanjun Xu, Qiaojun He, Ling Ding, Bo Yang
Journal: Acta Pharmaceutica Sinica B (2022)

Lipids have been found to modulate tumor biology, including proliferation, survival, and metastasis. With the new understanding of tumor immune escape that has developed in recent years, the influence of lipids on the cancer–immunity cycle has also been gradually discovered. First, regarding antigen presentation, cholesterol prevents tumor antigens from being identified by antigen presenting cells. Fatty acids reduce the expression of major histocompatibility complex class I and costimulatory factors in dendritic cells, impairing antigen presentation to T cells. Prostaglandin E2 (PGE2) reduce the accumulation of tumor-infiltrating dendritic cells. Regarding T-cell priming and activation, cholesterol destroys the structure of the T-cell receptor and reduces immunodetection. In contrast, cholesterol also promotes T-cell receptor clustering and relative signal transduction. PGE2 represses T-cell proliferation. Finally, regarding T-cell killing of cancer cells, PGE2 and cholesterol weaken granule-dependent cytotoxicity. Moreover, fatty acids, cholesterol, and PGE2 can improve the activity of immunosuppressive cells, increase the expression of immune checkpoints and promote the secretion of immunosuppressive cytokines. Given the regulatory role of lipids in the cancer–immunity cycle, drugs that modulate fatty acids, cholesterol and PGE2 have been envisioned as effective way in restoring antitumor immunity and synergizing with immunotherapy. These strategies have been studied in both preclinical and clinical studies.
Exposure to Static Magnetic and Electric Fields Treats Type 2 Diabetes
Authors: Calvin S. Carter, Sunny C. Huang, Charles C. Searby, Benjamin Cassaidy, Michael J. Miller, Wojciech J. Grzesik, Ted B. Piorczynski, Thomas K. Pak, Susan A. Walsh, Michael Acevedo, Qihong Zhang, Kranti A. Mapuskar, Ginger L. Milne, Antentor O. Hinton, Deng-Fu Guo, Robert Weiss, Kyle Bradberry, Eric B. Taylor, Adam J. Rauckhorst, David W. Dick, Vamsidhar Akurathi, Kelly C. Falls-Hubert, Brett A. Wagner, Walter A. Carter, Kai Wang, Andrew W. Norris, Kamal Rahmouni, Garry R. Buettner, Jason M. Hansen, Douglas R. Spitz, E. Dale Abel, Val C. Sheffield
Journal: Cell Metabolism (2022)
Pubertal Blockade and Subsequent Gender-Affirming Therapy
Authors: Carly Guss, Catherine M. Gordon
Journal: JAMA Network Open (2022)

Andrea L. Nos, MD; David A. Klein, MD, MPH; Terry A. Adirim, MD, MPH; Natasha A. Schvey, PhD; Elizabeth Hisle-Gorman, MSW, PhD; Apryl Susi, MS; Christina M. Roberts, MD, MPH
Use of US Food and Drug Administration Expedited Drug Development and Review Programs by Orphan and Nonorphan Novel Drugs Approved From 2008 to 2021
Authors: Andrea N. Monge, Daniel W. Sigelman, Robert J. Temple, Harinder Singh Chahal
Journal: JAMA Network Open (2022)

Importance The US Food and Drug Administration (FDA) has 4 programs that can be used alone or in combination to expedite drug availability: Accelerated Approval, Breakthrough Therapy, Fast Track, and Priority Review. Drugs using these programs can include novel drugs, which do not contain a previously FDA-approved active moiety, and orphan drugs, intended for diseases or conditions affecting fewer than 200 000 people; to date, no comprehensive evaluation of how these programs have been used in combination has been published. Objective To assess how often and in what combinations expedited programs are used in the development and review of approved novel biologics and small-molecule drugs, stratified by orphan drug status and indication. Design, Setting, and Participants This cross-sectional study evaluated all novel drugs that were FDA approved between January 1, 2008, and December 31, 2021. Main Outcomes and Measures The main outcome was the frequency with which expedited programs were used and in what combinations, stratified by orphan drug status and drug type (small molecule vs therapeutic biologic). The unit of analysis was the novel drug–indication pair because a drug can be approved for multiple indications, each of which may use a different expedited program or differ in orphan drug status. Results The study included 581 novel drug–indication pairs approved during the 14-year study period; 252 (43.4%) were orphan drugs, 139 (23.9%) were therapeutic biologics, and 442 (76.1%) were small-molecule drugs. Use of at least 1 expedited program increased from 11 of 26 drug-indication pairs (42.3%) in 2008 to 41 of 55 (74.5%) in 2021. Of the 363 approved drug-indication pairs using at least 1 expedited program, 225 (62.0%) were orphan drugs; at least 1 expedited program was used by 97 of the 139 approved biologic drugs (69.8%) and by 266 of the 442 approved small-molecule drugs (60.2%). Eighty-two of the 581 novel drug–indication pairs (14.1%) used the Accelerated Approval Program; of those, 65 (79.3%) were oncology drugs and 70 (85.4%) had an orphan designation. Conclusions and Relevance The study showed that use of the FDA’s expedited programs to bring novel drugs to market in the US increased from 2008 to 2021. The findings suggest that this trend is likely to continue.